scholarly journals Hyperin Alleviates Triptolide-Induced Ovarian Granulosa Cell Injury by Regulating AKT/TSC1/mTORC1 Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Fang You ◽  
Junyan Cao ◽  
Li Cheng ◽  
Xiaogu Liu ◽  
Li Zeng
Keyword(s):  
Signaling Pathway ◽  
Granulosa Cell ◽  
High Performance ◽  
Cell Injury ◽  
Ovarian Function ◽  
Interaction Network ◽  
Mtor Signaling ◽  
Network Pharmacology ◽  
Mtor Signaling Pathway ◽  
Mtorc1 Signaling

Premature ovarian insufficiency (POI) is characterized by the loss of ovarian function before 40 years of age and affects approximately 1% of women worldwide. Caragana sinica is a traditional Miao (a Chinese ethnic minority) medicine that improves ovarian function and follicular development. In the present study, we aimed to investigate the effect of active ingredients of C. sinica on POI and determine underlying mechanisms. Herein, the chemical composition of the C. sinica compound was analyzed using ultra-high-performance liquid chromatography, which identified hyperin (HR) as one of the main ingredients in C. sinica. Then, interaction targets of HR and POI were predicted and analyzed using network pharmacology and bioinformatics. The effect of HR on triptolide (TP)-induced granulosa cell injury was evaluated, and the underlying mechanism was explored based on bioinformatic results. A total of 100 interaction targets for POI and HR were obtained. The protein-protein interaction network of identified interaction targets emphasized the topological importance of AKT1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that HR might regulate POI by modulating the mechanistic target of rapamycin (mTOR) signaling pathway. In addition, the KEGG graph of the mTOR signaling pathway revealed that AKT phosphorylation inhibits the TSC1/2, while TSC1/2 activation inhibits the expression of mTORC1. The fundamental experiment revealed that HR increased proliferation, progesterone receptor levels, and estradiol levels decreased by TP in KGN cells. Additionally, HR alleviated TP-induced apoptosis and G1/G1 phase arrest in KGN cells. Western blotting demonstrated that HR increased the phosphorylation of AKT and mTORC1 and decreased TSC1 expression in TP-induced KGN cells. Collectively, our findings revealed that HR alleviates TP-induced granulosa cell injury by regulating AKT/TSC1/mTORC1 signaling, providing insight into the treatment of POI.

scholarly journals Integrated Network Pharmacology and Lipidomics to Reveal the Inhibitory Effect of Qingfei Oral Liquid on Excessive Autophagy in RSV-Induced Lung Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Lili Lin ◽  
Li An ◽  
Hui Chen ◽  
Lu Feng ◽  
Mengjiang Lu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Lung Inflammation ◽  
Mtor Signaling ◽  
Network Pharmacology ◽  
Mtor Signaling Pathway ◽  
Model Animal ◽  
Oral Liquid ◽  
Lipin 1 ◽  
Syncytial Virus

Background: Respiratory syncytial virus (RSV) can cause varying degrees of lung inflammation in children. Qingfei Oral Liquid (QF) is effective in treating childhood RSV-induced lung inflammation (RSV-LI) in clinics, but its pharmacological profiles and mechanisms remain unclear.Methods: This study combined network Pharmacology, lipidomics, pharmacodynamics, and pathway validation to evaluate the therapeutic mechanisms of QF. Using Cytoscape (v3.8.2) and enrichment analyses from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), a global view of the putative compound-target-pathway network was created. The corresponding lipidomic profiles were then used to detect differently activated lipids, revealing the metabolic pathway, using ultra-high-performance liquid chromatography linked to hybrid Quadrupole-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS). Meanwhile, the in vivo efficiency of QF, the enrichment pathway, and the excessive autophagy inhibition mechanisms were validated in RSV-infected mice models.Results: The network pharmacology results demonstrated 117 active compounds acted directly upon 101 core targets of QF against RSV-LI. The most significantly enriched pathway was the PI3K/Akt/mTOR signaling pathway (p < 0.05). In addition, untargeted lipidomics were performed, and it was revealed that higher lung levels of DAG 30:0, DAG 30:5, DAG 32:0, DAG 16:0_18:0, DAG 17:0_17:0, DAG 34:1, DAG 36:0, DAG 36:1 in the RSV-LI group were decreased after QF administration (FDR < 0.05, FC > 1.2). Lipin-1, a key enzyme in DAG synthesis, was increased in the RSV-LI mouse model. Animal experiments further validated that QF inhibited the PI3K/Akt/mTOR signaling pathway, with lower lung levels of phosphorylated PI3K, AKT and mTOR, as well as its related proteins of lipin-1 and VPS34 (p < 0.01). Finally, pharmacodynamic investigations indicated that QF reduced airway inflammation caused by excessive autophagy by decreasing lung levels of RSV F and G proteins, Beclin-1, Atg5, and LC3B II, IL-1 and TNF-α (p < 0.05).Conclusion: Lipidomic-based network pharmacology, along with experimental validation, may be effective approaches for illustrating the therapeutic mechanism of QF in the treatment of RSV-LI.

scholarly journals mTOR Signaling Pathway Regulates Sperm Quality in Older Men

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 629 ◽  
Author(s):  
Silva ◽  
Cabral ◽  
Correia ◽  
Carvalho ◽  
Sousa ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Sperm Quality ◽  
Older Men ◽  
Mtor Signaling ◽  
Paternal Age ◽  
Signaling Proteins ◽  
Mtor Signaling Pathway ◽  
Mtorc1 Signaling ◽  
The Impact

: Understanding how age affects fertility becomes increasingly relevant as couples delay childbearing toward later stages of their lives. While the influence of maternal age on fertility is well established, the impact of paternal age is poorly characterized. Thus, this study aimed to understand the molecular mechanisms responsible for age-dependent decline in spermatozoa quality. To attain it, we evaluated the impact of male age on the activity of signaling proteins in two distinct spermatozoa populations: total spermatozoa fraction and highly motile/viable fraction. In older men, we observed an inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) in the highly viable spermatozoa population. On the contrary, when considering the entire spermatozoa population (including defective/immotile/apoptotic cells) our findings support an active mTORC1 signaling pathway in older men. Additionally, total spermatozoa fractions of older men presented increased levels of apoptotic/stress markers (e.g., cellular tumor antigen p53-TP53) and mitogen-activated protein kinases (MAPKs) activity. Moreover, we established that the levels of most signaling proteins analyzed were consistently and significantly altered in men more than 27 years of age. This study was the first to associate the mTOR signaling pathway with the age impact on spermatozoa quality. Additionally, we constructed a network of the sperm proteins associated with male aging, identifying TP53 as a central player in spermatozoa aging.

scholarly journals Melatonin regulates chicken granulosa cell proliferation and apoptosis by activating the mTOR signaling pathway via its receptors

2020 ◽  
Vol 99 (11) ◽  
pp. 6147-6162
Author(s):  
Er-ying Hao ◽  
De-He Wang ◽  
Li-yun Chang ◽  
Chen-xuan Huang ◽  
Hui Chen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Granulosa Cell ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Proliferation And Apoptosis

scholarly journals Time-Dependent Changes in Hepatic Sphingolipid Accumulation and PI3K/Akt/mTOR Signaling Pathway in a Rat Model of NAFLD

2021 ◽  
Vol 22 (22) ◽  
pp. 12478
Author(s):  
Klaudia Sztolsztener ◽  
Karolina Konstantynowicz-Nowicka ◽  
Ewa Harasim-Symbor ◽  
Adrian Chabowski
Keyword(s):  
Signaling Pathway ◽  
High Performance ◽  
Glucose Transporter ◽  
Significant Inhibition ◽  
Mtor Signaling ◽  
Time Dependent ◽  
Standard Diet ◽  
Mtor Signaling Pathway ◽  
Akt Phosphorylation ◽  
Male Wistar Rats

Increased lipid bioavailability in a diet favors lipid accumulation, enhancing hepatic lipotoxicity and contributing to insulin resistance (IR) development. The aim of our study was to examine time-dependent alterations in the intrahepatic content of sphingolipids and insulin signaling pathway in rats fed a high-fat diet (HFD). The experiment was conducted on male Wistar rats receiving a standard diet or HFD for five weeks. At the end of each experimental feeding week, liver sphingolipids were determined using high-performance liquid chromatography. The expression of proteins from the sphingolipid pathway and glucose transporter expression were assessed by Western blot. The content of phosphorylated form of proteins from the insulin pathway was detected by a multiplex assay kit. Our results revealed that HFD enhanced hepatic ceramide deposition by increasing the expression of selected proteins from sphingomyelin and salvage pathways in the last two weeks. Importantly, we observed a significant inhibition of Akt phosphorylation in the first week of HFD and stimulation of PTEN and mTOR phosphorylation at the end of HFD. These changes worsened the PI3K/Akt/mTOR signaling pathway. We may postulate that HFD-induced reduction in the insulin action in the time-dependent matter was exerted by excessive accumulation of sphingosine and sphinganine rather than ceramide.

scholarly journals LncRNA Hoxb3os protects podocytes from high glucose-induced cell injury through autophagy dependent on the Akt-mTOR signaling pathway

2021 ◽  
Author(s):  
Juan Jin ◽  
Jianguang Gong ◽  
Li Zhao ◽  
Yiwen Li ◽  
Qiang He
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
High Glucose ◽  
Cell Injury ◽  
Damage Model ◽  
Mtor Signaling ◽  
Cell Counting ◽  
Tunel Staining ◽  
Mtor Signaling Pathway ◽  
Potential Biomarker

Background: Diabetic nephropathy (DN) is in the first place of the causes that lead to end-stage renal disease in the world. Thus, it is urgent to develop a novel diagnostic or therapeutic strategy that could stop the progression of diabetic nephropathy. Methods: RNA-sequencing was conducted in high glucose (HG)-treated MPC5 cells (podocytes). Cell morphology was examined under a light microscope. Upon high-glucose challenge, the effects of lncRNA Hoxb3os overexpression on MPC5 cells apoptosis, viability, autophagy and Akt-mTOR signaling were evaluated using flow cytometry, Cell Counting Kit-8, qRT-PCR, and Western blotting. TUNEL staining and ELISA were performed to confirm the establishment of DN model in db/db mice. Results: High-glucose exposure dramatically altered lncRNA expression profile in MPC5 cells (fold change>2), including 305 upregulated lncRNAs and 451 downregulated lncRNAs. LncRNA Hoxb3os expression was significantly reduced in the HG-induced podocyte damage model, as well as in the renal tissues from db/db mice with spontaneous DN. Overexpression of Hoxb3os significantly reduced the apoptosis rate and increased the viability of MPC5 cells under HG conditions. Further study revealed that exogenous Hoxb3os increased autophagy level in HG-exposed MPC5 cells via abrogating Akt-mTOR signaling pathway and that the process was possibly implicated in the upregulation of SIRT1. Conclusion: LncRNA Hoxb3os protected podocytes from HG-induced damage by regulating Akt-mTOR pathway and cell autophagy. Thus, lncRNA Hoxb3os appears as a potential biomarker in the diagnosis and treatment of DN in the future.

scholarly journals Burn Ointment Promotes Cutaneous Wound Healing by Modulating the PI3K/AKT/mTOR Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Dali Gan ◽  
Qiyuan Su ◽  
Hanwen Su ◽  
Li Wu ◽  
Jun Chen ◽  
...  
Keyword(s):  
Wound Healing ◽  
Signaling Pathway ◽  
High Performance ◽  
Scientific Evidence ◽  
Latency Period ◽  
Analgesic Efficacy ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Hot Plate ◽  
Anti Inflammatory

Burn ointment (BO) is a clinically useful medicine for the treatment of burns and scalds. However, there is no enough scientific evidence to report the effect of BO on wound healing and its analgesic and anti-inflammatory efficacy. The aim of this work was to evaluate the anti-inflammatory and analgesic efficacy of BO and to reveal the potential wound healing properties and related mechanisms of BO. In this work, the content of active ingredients of BO was determined by high-performance liquid chromatography (HPLC). Two animal models of inflammation were used to study its anti-inflammatory activity, and a hot plate method was used to evaluate its analgesic effect. In addition, mouse incision and rat burn models were used to investigate the effect of BO on the anti-inflammatory and wound healing mechanisms. The results showed that BO was safe for topical application, and BO could significantly inhibit auricular swelling in mice and paw swelling in rats and significantly prolong the latency period of paw licking in the hot plate experiment in mice. It can also accelerate wound healing and repair scars by promoting the formation of new epithelial tissues in rat burn models. In addition, BO significantly downregulated the serum level of TNF-α and significantly increased the serum levels of VEGF and TGF-β1. Also, BO promoted the expression of collagen I and increased the ratio in p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR pathways. Our results demonstrate the safety and efficacy of BO and suggest that activation of the PI3K/AKT/mTOR signaling pathway may play an important role in the promotion of wound healing by BO.

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